Objective: To determine the physical and chemical stability of anti-tuberculosis fixed-dose combinations (FDC) of rifampicin (RMP), isoniazid (INH), pyrazinamide (PZA) and ethambutol (EMB) sold on the Indian market.
Methods: The products were stored for 3 months under ICH/WHO accelerated conditions (40 degrees C / 75% RH), with and without the original packaging in the presence and absence of light.
Results: The initial RMP, INH and PZA content was found to be within the range of 90-110% of the label claim. However, the products were found to have some chemical instability even initially; one of the tablets also showed physical instability. Under accelerated conditions, the unpackaged products underwent severe changes, whereas both physical and chemical changes were also observed in the packaged formulations. The physical changes were stronger under lighted conditions. A significant finding is that PZA and perhaps EMB may play a catalytic role in the interaction between INH and RMP.
Conclusion: This study suggests that, unless they are packed in barrier packaging, anti-tuberculosis FDC formulations should be considered unstable, and due consideration should be given to their development pharmaceutics, packaging and stability testing.